Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 May 15;17(5):105148.
doi: 10.4251/wjgo.v17.i5.105148.

Hepatitis B core-related antigen as a predictive biomarker for recurrence in primary hepatocellular carcinoma: A meta-analysis

Ling-Bo Liang  1 , Hai-Jun Zhang  2 , Feng Liu  1 , Qiao-Li Su  3
Affiliations

Hepatitis B core-related antigen as a predictive biomarker for recurrence in primary hepatocellular carcinoma: A meta-analysis

Ling-Bo Liang et al. World J Gastrointest Oncol. .

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies, with high recurrence rates after treatment. Identifying reliable biomarkers for predicting recurrence is essential for improving patient outcomes. Hepatitis B core-related antigen (HBcrAg) has shown potential as a predictive marker for HCC recurrence.

Aim: To evaluate the association between HBcrAg levels and the risk of HCC recurrence.

Methods: A systematic review was conducted following PRISMA guidelines. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched without restrictions on date or language. Observational studies reporting hazard ratios (HRs) for HBcrAg as a predictor of HCC recurrence were included. Data extraction and quality assessment were performed independently by two reviewers. Statistical analyses used a random-effects model to account for heterogeneity (I² ≥ 50%), and sensitivity analysis was performed to ensure the robustness of the results.

Results: A total of 1339 articles were initially identified, and 17 studies were included in the final meta-analysis after screening. The pooled analysis showed a significant association between elevated HBcrAg levels and HCC recurrence (HR = 4.42, 95% confidence interval: 3.43-5.41) with substantial heterogeneity (I² = 92.6%). Subgroup analysis revealed higher pooled HRs in studies with ≥ 500 participants (HR = 4.18) and HBcrAg cut-offs ≥ 4.0 LogU/mL (HR = 5.29). Studies with ≥ 10 years of follow-up showed a lower HR (2.89) compared to those with < 10 years (3.27). Patients treated with nucleos(t)ide analogs had a pooled HR of 1.98, while those without nucleos(t)ide analog had a higher HR of 3.87. Sensitivity analysis confirmed the robustness of the results, with no significant publication bias detected.

Conclusion: This meta-analysis provides strong evidence that elevated HBcrAg levels are associated with an increased risk of HCC recurrence. HBcrAg may serve as a valuable biomarker for predicting recurrence, aiding personalized management and surveillance strategies for HCC patients.

Keywords: Hepatitis B core-related antigen; Hepatocellular carcinoma; Meta-analysis; Predictive biomarker; Recurrence.

PubMed Disclaimer

Conflict of interest statement

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Figures

Figure 1
Figure 1
Flowchart showing the process of study selection for inclusion in the meta-analysis.
Figure 2
Figure 2
Forest plot displaying the association between hepatitis B core-related antigen and recurrence of primary hepatocellular carcinoma. CI: Confidence interval.
Figure 3
Figure 3
Sensitivity analysis graph evaluating the stability of the meta-analysis findings. CI: Confidence interval.
Figure 4
Figure 4
Funnel plot assessing the presence of publication bias among studies included in the meta-analysis.
See this image and copyright information in PMC

References

    1. Wang Z, Qin H, Liu S, Sheng J, Zhang X. Precision diagnosis of hepatocellular carcinoma. Chin Med J (Engl) 2023;136:1155–1165. - PMC - PubMed
    1. Nevola R, Ruocco R, Criscuolo L, Villani A, Alfano M, Beccia D, Imbriani S, Claar E, Cozzolino D, Sasso FC, Marrone A, Adinolfi LE, Rinaldi L. Predictors of early and late hepatocellular carcinoma recurrence. World J Gastroenterol. 2023;29:1243–1260. - PMC - PubMed
    1. Chen S, Huang C, Liao G, Sun H, Xie Y, Liao C, Wang J, He M, Hu H, Dai Z, Ren X, Zeng X, Lin Z, Zhang GP, Xie W, Shen S, Li S, Peng S, Kuang DM, Zhao Q, Duda DG, Kuang M. Distinct single-cell immune ecosystems distinguish true and de novo HBV-related hepatocellular carcinoma recurrences. Gut. 2023;72:1196–1210. - PubMed
    1. Jin H, Wang H, Li G, Hou Q, Wu W, Liu F. Risk factors for early postoperative recurrence in single and small hepatitis B virus-associated primary hepatocellular carcinoma. J Int Med Res. 2020;48:300060520961260. - PMC - PubMed
    1. Inoue T, Tanaka Y. The Role of Hepatitis B Core-Related Antigen. Genes (Basel) 2019;10:357. - PMC - PubMed

LinkOut - more resources